Inappropriate preinjury warfarin use in trauma patients: A call for a safety initiative.

INTRODUCTION: Warfarin continues to be widely prescribed for a variety of conditions. It has been shown that preinjury warfarin may worsen outcomes in trauma patients. We hypothesized that a substantial proportion of injured patients seen at our institution were receiving preinjury warfarin for inappropriate indications and that a significant number of such patients had subtherapeutic or supratherapeutic international normalized ratios as well as increased mortality. MATERIALS AND METHODS: A retrospective review of registry data from a Level I trauma center was conducted for the period from January 2004 to July 2013. Included were patients aged ≥22 years (based on the youngest recorded patient on warfarin in this study). Abstracted variables included patient age, Injury Severity Score (ISS), Maximum Abbreviated Injury Score for Head (MAISH), mortality, hospital length of stay (HLOS), indication(s) for anticoagulant therapy, admission Glasgow Coma Scale (GCS), and admission international normalized ratio (INR). Suitability of warfarin indication(s) was determined using the most recent American College of Chest Physicians (ACCP) Guidelines. Inappropriate warfarin administration was defined as use inconsistent with these guidelines. For outcome comparisons, a case-control design with 1:1 ratio was used, matching patients taking preinjury warfarin to a random sample of trauma patients who were not taking warfarin. Severe traumatic brain injury (sTBI) was defined as MAISH ≥4. RESULTS: A total of 700 out of 14,583 patients aged ≥22 years were receiving preinjury warfarin (4.8% incidence, WG). This group was age- and ISS-matched with 700 patients (4.8% total sample) who were not taking warfarin (NWG) in a total case-control sample of 1,400. The two groups were similar in age, gender, ISS, and initial GCS. According to the ACCP guidelines, 115/700 (16.4%) patients in the warfarin group were receiving anticoagulation for inappropriate indications. Nearly 65% of the patients were outside of their intended INR therapeutic window (43.4% subtherapeutic, 21.6% supratherapeutic). Overall, median HLOS was greater among patients taking preinjury warfarin (4 days vs 2 days, P < 0.010). Mortality was higher in the WG (7.4% or 52/700) than in the NWG (1.9% or 13/700, P < 0.010). Patients with sTBI in the WG had significantly greater mortality (12.8% or 34/266) than those with sTBI in the NWG (5.3% or 9/169, P < 0.013). CONCLUSION: A significant proportion of trauma patients admitted to our institution were noted to take warfarin for inappropriate indications. Moreover, many patients taking warfarin had either subtherapeutic or supratherapeutic INR. Although warfarin use did not independently predict mortality, preinjury warfarin use was associated with greater mortality and HLOS in the subset of patients with sTBI. Safety initiatives directed at better initiation and management of warfarin are needed.

Socioeconomic status and lifestyle behaviours in cancer survivors: smoking and physical activity.

PURPOSE: Smoking cessation and increased physical activity (pa) have been linked to better outcomes in cancer survivors. We assessed whether socioeconomic factors influence changes in those behaviours after a cancer diagnosis. METHODS: As part of a cross-sectional study, a diverse group of cancer survivors at the Princess Margaret Cancer Centre (Toronto, ON), completed a questionnaire about past and current lifestyle behaviours and perceptions about the importance of those behaviours with respect to their health. The influence of socioeconomic indicators on smoking status and physical inactivity at 1 year before and after diagnosis were assessed using multivariable logistic regression with adjustment for clinico-demographic factors. RESULTS: Of 1222 participants, 1192 completed the smoking component. Of those respondents, 15% smoked before diagnosis, and 43% of those smokers continued to smoke after. The proportion of survivors who continued to smoke increased with lower education level (p = 0.03). Of the 1106 participants answering pa questions, 39% reported being physically inactive before diagnosis, of whom 82% remained inactive afterward. Survivors with a lower education level were most likely to remain inactive after diagnosis (p = 0.003). Lower education level, household income, and occupation were associated with the perception that pa had no effect or could worsen fatigue and quality of life (p ≤ 0.0001). CONCLUSIONS: In cancer survivors, education level was a major modifier of smoking and pa behaviours. Lower socioeconomic status was associated with incorrect perceptions about pa. Targeting at-risk survivors by education level should be evaluated as a strategy in cancer survivorship programs.

Is laparoscopic repair of incarcerated abdominal hernias safe? Analysis of short-term outcomes.

BACKGROUND: There is a paucity of literature surrounding the safety and feasibility of laparoscopic repair for acutely incarcerated abdominal hernias. The objective of this study was to compare the 30-day morbidity and mortality between laparoscopic and open repairs of incarcerated abdominal hernias. METHODS: A retrospective cohort study was conducted using data from the National Surgery Quality Improvement Program from 2005 to 2012. The study population was selected using ICD-9 diagnostic codes describing abdominal hernias with obstruction, but without gangrene. Cases with documented bowel resection were excluded. Group classification was based on CPT coding. Study outcomes included the 30-day major complication, reoperation and mortality rates. Multivariable logistic regression models were used to adjust for confounding for all study outcomes. RESULTS: A total of 2688 and 15,562 patients were in the laparoscopic and open group, respectively. After adjustment for clinically relevant confounders, laparoscopic surgery was associated with a significantly lower 30-day infectious (OR 0.36, p < 0.001, 95 % CI 0.23-0.56) and serious complication rates (OR 0.66, p < 0.001, 95 % CI 0.55-0.80). However, there was no statistical difference with respect to the 30-day reoperation (OR 0.81, p = 0.28, 95 % CI 0.56-1.18) or mortality rates (OR 0.94, p = 0.80, 95 % CI 0.58-1.53). CONCLUSIONS: Patients with incarcerated abdominal hernias who underwent laparoscopic repair had a significantly lower 30-day morbidity compared to patients with open repair. Although the 30-day reoperation and mortality rates were also lower, there was no statistically significant difference. Laparoscopic surgery appears to be safe in the management of select incarcerated abdominal hernias.

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format.

Prophylactic PPI help reduce marginal ulcers after gastric bypass surgery: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Marginal ulceration after gastric bypass surgery is a recognized complication and has been reported in 1-16% of patients. There is evidence that acidity may play a role in the disease pathophysiology and it is a common practice for bariatric surgeons to begin a prophylactic course of proton pump inhibitors (PPI), postoperatively. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched using the most comprehensive timeline for each database up to January 2012. Studies that included patients undergoing gastric bypass who received a prophylactic course of PPI postoperatively were eligible. Two reviewers independently selected trials and extracted data. The primary outcome was the incidence of marginal ulcers diagnosed on the basis of endoscopic findings. Inverse variance random effects models were used to estimate odds ratio (OR) and weighted proportion of ulcers. Odds ratio and weighted pooled proportion with corresponding 95% confidence intervals (CI) are reported. RESULTS: The strategic search identified 167 citations. A total of seven studies involving 2,917 participants were eligible for inclusion and 2,114 were used for analysis. The weighted pooled proportion of ulcer formation in PPI groups including all seven studies (four single group cohort studies and PPI arm of three cohort studies) was 5.0% [95% CI 2-10%] (N = 1,407). The OR of marginal ulcer formation comparing PPI to no PPI for three comparative cohort studies was 0.50 [95% CI 0.28-0.90, p = 0.02] (N = 1,022) with low heterogeneity (I(2) = 12%) showing that the PPI group significantly experienced twice less ulceration with PPI treatment compared to no PPI treatment. CONCLUSION: This finding suggests a significant incremental benefit of prophylactic PPI in reducing marginal ulcer after gastric bypass surgery. Prospective randomized trials are needed to further define the role of PPI following gastric bypass surgery.

A comparison of anaesthetic recoveries in cats following induction with either alfaxalone or ketamine and diazepam.

AIM: To determine if cats anaesthetised with alfaxalone have different recoveries to cats anaesthetised with a combination of ketamine and diazepam. METHODS: Anaesthesia for ovariohysterectomy was induced in cats with either alfaxalone (n=23) or a combination of ketamine and diazepam (n=22). All cats were premedicated with combinations of acepromazine and morphine. Recoveries were scored using a categorical grading scheme applied to 18 parameters over 60 minutes following extubation. The parameters scored covered movement, sensitivity to touch, sound and light, body position, sneezing and vocalisation. One person scored all recoveries and they were blinded to the induction drug used. Scores were compared between drugs at different times using the Kruskal-Wallis rank sum test. RESULTS: Recovery scores were not normally distributed. Analysis of the data using the Kruskal-Wallis rank sum test revealed that cats induced with alfaxalone showed an increase in recovery scores at 5 minutes for pawing at the head (p=0.001). No parameters differed significantly at 10 and 20 minutes. For cats anaesthetised with ketamine and diazepam there was an increase at 30 minutes in pacing, jerky sudden movements, unsettledness and increased sensitivity to touch at the surgical site and on the head (p≤0.01). At 60 minutes cats anaesthetised with ketamine and diazepam still showed an increase in unsettledness compared to those cats anaesthetised with alfaxalone (p=0.005). CONCLUSIONS: The results suggest that recoveries of cats following alfaxalone induction are significantly different to recoveries after induction with ketamine and diazepam. Overall, cats induced with ketamine and diazepam had more active and unsettled recoveries than alfaxalone over the 60-minute period observed. CLINICAL RELEVANCE: Cats recovering from alfaxalone anaesthesia have more settled recoveries than cats recovering from ketamine and diazepam anaesthesia. If a quiet settled recovery is desired following a surgical procedure, alfaxalone is likely to be a better choice than ketamine and diazepam.

An evaluation of intraoperative digital specimen mammography versus conventional specimen radiography for the excision of nonpalpable breast lesions.

BACKGROUND: This study examined the impact of intraoperative digital specimen mammography (IDSM) compared with conventional specimen radiography (CSR) for nonpalpable breast lesions in patients undergoing breast-conserving surgery (BCS). METHODS: In this retrospective cohort study, 201 consecutive image-detected nonpalpable breast lesions underwent BCS after preoperative localization and specimen radiography. Data on patient, tumor, and surgical factors were collected. RESULTS: CSR was performed in 105 patients and IDSM was used in 96 patients. Patient and tumor factors were similar in both groups. Using univariate analysis, CSR resulted in more positive margins (19% vs 6.2%; P = .012). Rates of cavity margin resection, reoperation, and operative times were similar for CSR and IDSM. Independent predictors of positive margins on multivariable analysis were use of CSR, microcalcifications on mammography, the need for bracketing for localization, and no cavity margin excision (all P < .05). CONCLUSIONS: In this study, the use of IDSM resulted in fewer positive margins after BCS, although operative times were similar.

Eco-health evaluation for the Shanghai metropolitan area during the recent industrial transformation (1990-2003).

Shanghai is a cosmopolitan city and one of the most important economic centers in China, but is saddled with serious environmental problems resulting from a recent industrial transformation. This paper examines the interactive relationships between economic growth, eco-efficiency of urban metabolism, and environmental performance of the Shanghai metropolitan area since the 1990s using 15 indicators. This study has revealed an enhanced eco-efficiency of water and energy use as well as an improved overall environmental quality in the central urban districts of Shanghai. Both TGDP (total GDP) and GDP per capita increased rapidly at the annual rate of 16.28% and 15.91%, respectively. In contrast, energy consumed per 10,000 RMB YUAN GDP (ECG), water consumed per 10,000 RMB YUAN GDP (WCG), wastewater discharged per 10,000 RMB YUAN GDP (WWDG), and waste gases emitted per 10,000 RMB YUAN GDP (WGEG) decreased at the annual rate of 9.34%, 10.69%, 14.57%, and 8.52%, respectively. The rapid decline in ECG, WCG, WWDG, and WGEG indicates an enhanced eco-efficiency of urban metabolism. However, uncontrolled emission of wastes from domestic instead of industrial sources adversely affected the overall environmental quality. In addition, suburban areas have undergone rapid economic growth at the cost of human health deterioration, as measured by mortalities and relative mortality ratios of three major diseases (tumor, respiratory disease, and trauma/toxicosis). With Shanghai serving as the "locomotive" driving the economy of the Yangtze River Basin, effective pollution control policies and a network of regional coordination are urgently needed in the globalization and ecological security of the entire area.

Understanding the Concept of 'Family History' in Black Asthmatic Children

Background. Despite the fact that 71.6 of children at Chris Hani Baragwanath Hospital (CHBH) Asthma Clinic in Soweto; Johannesburg were found to have one or more positive skin-prick tests (SPTs) to common aero-allergens; they reported a low rate of positive family history for atopic conditions (22.2reason(s) why a positive family history has been found so seldom in these children. Methods. A random group of parents of the atopic asthmatic children attending the CHBH Children's Asthma Clinic completed a detailed questionnaire regarding their atopic status. Skin-prick testing was performed. Results. Fifty-four sets of parents and 15 single mothers were studied. Of the 48 atopic children; 37 (77). In the past this has minimised the importance of family history in determining the nature of chest symptoms in children in this population group; suggesting that some new environmental exposure; rather than the established familial factor; was creating the allergic milieu in this group. Objective. To determine the predictive value of a family history of symptoms of atopic disease (and allergy) by seeking evidence for this condition in the parents of asthmatic children attending the CHBH Children's Asthma Clinic; and the ) had at least 1 parent with a positive SPT. Fifty-five per cent of mothers had a positive SPT; while 48 of fathers had at least 1 positive SPT. Seven of 69 mothers (10) had a definitive diagnosis of asthma. Of these; 5 (71) were SPT-positive. Only 3 of the fathers (5.5) had asthma. All had positive SPTs. However; if all the symptoms suggestive of asthma; namely chronic cough or wheeze; were taken into account; the number of potential atopic fathers and mothers increased to 10 (19) and 18 (26) respectively. Conclusion. Simple questioning for family history of atopic disease is therefore not a good predictor of atopy in offspring in this cohort of patients. In order to get maximal yield from this question; parents must rather be asked about specific symptoms suggestive of asthma and/or allergic rhinitis

Practical three color live cell imaging by widefield microscopy.

Live cell fluorescence microscopy using fluorescent protein tags derived from jellyfish and coral species has been a successful tool to image proteins and dynamics in many species. Multi-colored aequorea fluorescent protein (AFP) derivatives allow investigators to observe multiple proteins simultaneously, but overlapping spectral properties sometimes require the use of sophisticated and expensive microscopes. Here, we show that the aequorea coerulescens fluorescent protein derivative, PS-CFP2 has excellent practical properties as a blue fluorophore that are distinct from green or red fluorescent proteins and can be imaged with standard filter sets on a widefield microscope. We also find that by widefield illumination in live cells, that PS-CFP2 is very photostable. When fused to proteins that form concentrated puncta in either the cytoplasm or nucleus, PSCFP2 fusions do not artifactually interact with other AFP fusion proteins, even at very high levels of over-expression. PSCFP2 is therefore a good blue fluorophore for distinct three color imaging along with eGFP and mRFP using a relatively simple and inexpensive microscope.

Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much ciprofloxacin is enough?

OBJECTIVE: To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis. DESIGN: Open and prospective. SETTING: Tertiary referral multi-disciplinary ICU. PATIENTS: Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years). INTERVENTIONS: Timed blood samples were taken for pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then between days 6-8. MEASUREMENTS AND RESULTS: Ciprofloxacin serum levels were measured by high performance liquid chromatography. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (C(max)) for group A were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (C(min)) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3, 18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. C(max) in these patients were higher than the average C(max). The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease. CONCLUSIONS: There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.

Do steroids prevent reintubation in children with laryngotracheobronchitis?

BACKGROUND: Classic laryngotrachoebronchitis (LTB) is an inflammatory process, with oedema and secretions that involve the entire laryngotracheobronchial tree. The severity of lower airway disease in African children with LTB has previously been documented. The aim of the present study was to determine whether steroids prevent reintubation in African children with classic LTB. METHOD AND RESULTS: The study was a retrospective analysis from January 1993 to December 1996. Eighty-two black children with LTB were mechanically ventilated in the intensive care unit (ICU). By univariate regression, the estimated B coefficients for variables such as age, pneumonia, days of intubation, arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratio, atelectasis and antibiotic use were not statistically significant (P > 0.05) as predictors for reintubation. Using multiple regression (all independent variables in combination), none of the variables acted as predictors of reintubation (P = 0.25). Steroids were shown to have no effect alone or in association with other variables in altering reintubation rates. An increase in the days of intubation showed a tendency towards reintubation (P = 0.06) in the univariate analysis (odds ratio 1.00-1.14), but showed no statistically significant difference in multivariate analysis. Of the variables used as predictors of reintubation, none acted either as a preventive factor or as a risk factor. CONCLUSION: The present results suggest that steroids should not be recommended at any stage in treatment of intubated patients with classic LTB. Prospective studies should evaluate the major risk factors for reintubation: duration of intubation, trauma to the airway at intubation and during ICU stay, and dose and timing of steroids. They should also evaluate whether upper airway disease is present alone or in association with lower airway disease.

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.

Analgesia and sedation in the critically ill--a practical approach.

Advancements in intensive care therapy have progressed rapidly over the last two decades. Associated with this have been scientifically unsubstantiated sedation and analgesia practices in the intensive care unit. There is little consensus as to which agents are the most suitable, let alone when and how to use them. There are few, if any, placebo-controlled trials involving sedative drugs in critically ill patients. In an analysis of the literature, we have attempted to present a practical approach to sedation and analgesia practices in the critically ill patient. The aim is to present a framework upon which medical personnel managing critically ill patients can develop a strategy for their own circumstances.

Pharmacokinetic profiles of high-dose intravenous ciprofloxacin in severe sepsis. The Baragwanath Ciprofloxacin Study Group.

The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6. 01 +/- 1.93 mg/liter; D2, 6.68 +/- 2.01 mg/liter; and D6 to D8 6.45 +/- 1.54 mg/liter. Trough levels were as follows: D0, 0.6 +/- 0.5 mg/liter; D2, 0.7 +/- 0.4 mg/liter; and D6 to D8 0.6 +/- 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 +/- 3.8 mg . h/liter; D2, 16.8 +/- 5.4 mg . h/liter; and D6 to D8, 15.5 +/- 4.7 mg . h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.

Severe soft-tissue infections--a diagnostic challenge. The need for early recognition and aggressive therapy.

OBJECTIVES: This article was written to highlight the difficulty in diagnosing necrotising fasciitis (NF) and in differentiating it from other severe soft-tissue infections, and to stress the need for early aggressive therapy in all severe soft-tissue infections. METHOD: Four cases of severe soft-tissue infection admitted to Baragwanath Hospital Intensive Care Unit between January 1993 and March 1996 are reported, presenting the relevant clinical features. RESULTS: The clinical diagnosis of NF when used alone was found to be unreliable and the diagnosis appeared to be made late in the course of the disease. Late diagnosis makes intensive care (largely supportive therapy) of limited value. CONCLUSION: Astute clinical awareness and prompt therapy for severe soft-tissue infections are needed to enable the early diagnosis of these syndromes and thus prevent their serious sequelae. This should include a thorough knowledge of these conditions and predisposing risk factors. For comparative purposes specific defining clinical criteria are required. Even with full intensive care support, severe soft-tissue infections are associated with a significant mortality rate.

Naive alloreactive CD8 T cells are activated by purified major histocompatibility complex class I and antigenic peptide.

In this report, we demonstrate stimulation of T cell receptor (TCR) transgenic CD8 T cells by isolated major histocompatibility complex (MHC) class I H-2Ld complexes and antigenic peptide. This is the first demonstration of CD8 T cells activated by MHC and antigenic peptide in the absence of antigen priming. Furthermore, isolated MHC and a potent peptide antigen can stimulate phenotypically naive CD44- T cells to become CTL effectors and to produce interleukin-2 in nanogram per milliliter amounts. These results demonstrate that particular TCR antigen pairs may overcome the need for specialized antigen-presenting cells and have implications for mechanisms of autoimmunity and tolerance induction.

Accuracy of pulse oximetry in pigmented patients.

OBJECTIVE: Prospective assessment of the accuracy of three pulse oximeters and two probe sites in darkly pigmented critically ill patients under clinical conditions. PATIENTS AND METHODS: One hundred consecutive, darkly pigmented critically ill adult patients with arterial lines in situ were studied. Patients were excluded if the haemoglobin concentration was less than 7 g/dl and carboxyhaemoglobin or methaemoglobin levels exceeded 2%. Pigmentation was objectively quantified with a portable EEL reflectance spectrophotometer (Evans Electroselenium Company, Diffusion Systems Limited, London). Reflectance was measured at nine wavelengths. RESULTS: The degree of pigmentation as measured by percentage reflectance closely matched that of a control group of black Africans from a pigmentation study. The limits of agreement (2.6% to 5.8%), precision and bias values between pulse oximeter and co-oximeter readings fell within a narrow range. The 95% confidence intervals of the limits of agreement reflected a small variation in the difference between pulse oximeter and co-oximeter readings. These small differences were not clinically significant in the pigmented patients who were enrolled in the study. CONCLUSION: The accuracy of pulse oximetry is not adversely affected by skin pigmentation, and it remains a useful oxygenation monitoring device in darkly pigmented patients.